Previous work in this laboratory by Dr. Reichle, and colleagues, has shown that rats with a portacaval shunt have a significantly lower incidence of mammary tumor after dimethylbenz (a) anthracene (DMBA) treatment. This proposal is concerned with investigating possible involvement of metabolic and immunological factors in the anti-tumor effect of portacaval shunt in rats treated with a tumor-inducing dose of DMBA and to investigate the possible anti-tumor effect of a portacaval shunt in other tumor systems including transplantable hepatomas (in collaboration with Dr. Harold Morris, Howard University). Metabolic studies will consist of: 1) qualitative studies on the types of metabolites formed from DMBA by homogenates of liver from rats which do or do not have a portacaval shunt and which have or have not been pretreated with DMBA, and 2) quantitative studies on the rate of hydroxylation of benzo (a) pyrene by homogenates of liver from groups of rats similar to those used in 1). To determine whether tumor resistance is due to immunologic factors, rats with and without a shunt will be studied. Our results show that a large increase in liver BP hydroxylase in 7 week females (but not in 11 week females) and a large decrease in liver BP hydroxylase in 7 week males occurs following portacaval shunting and is accompanied by proportional changes in the level of microsomal P450 cytochrome in the livers of these animals. These results indicate that the liver microsomal aryl hydrocarbon hydroxylase system in the seven week old female is under different control mechanisms or is different in nature, compared to that in the ll week old female and 7 week old male. This may be involved in the higher susceptibility of 7 week females to breast tumor induction by DMBA and may play a role in the resistance to DMBA carcinogenesis produced by the portacaval shunt. BIBLIOGRAPHIC REFERENCES: Noval, Joseph J., Obando, Marcelo, Rao, Narasimha, Reichle, Rose Marie and Reichle, Frederick, A.: Promotion or Inhibition of Breast Carcinoma in Holtzman Rats Treated with Fetal Tissues and 7, 12-Dimethylbenzanthracene (DMBA). Fed. Proc., 35(3), 2311, 1976.